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Trends Pharmacol Sci. 2017 Sep;38(9):837-847. doi: 10.1016/j.tips.2017.05.010. Epub 2017 Jun 22.

Applying Structure-Based Drug Design Approaches to Allosteric Modulators of GPCRs.

Author information

1
Heptares Therapeutics Ltd, Biopark, Welwyn Garden City, UK.
2
Heptares Therapeutics Ltd, Biopark, Welwyn Garden City, UK. Electronic address: fiona.marshall@heptares.com.

Abstract

Structural insights have been revealed from X-ray co-complexes of a range of G protein-coupled receptors (GPCRs) and their allosteric ligands. The understanding of how small molecules can modulate the function of this important class of receptors by binding to a diverse range of pockets on and inside the proteins has had a profound impact on the structure-based drug design (SBDD) of new classes of therapeutic agents. The types of allosteric pockets and the mode of modulation as well as the advantages and disadvantages of targeting allosteric pockets (as opposed to the natural orthosteric site) are considered in the context of these new structural findings.

KEYWORDS:

G protein-coupled receptor; X-ray crystallography; allosteric modulator; structure-based drug design

PMID:
28648526
DOI:
10.1016/j.tips.2017.05.010
[Indexed for MEDLINE]

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